Benign and Malignant Thyroid Disease Among Those Exposed as Children to Fallout from the Chornobyl Accident The Chernobyl nuclear reactor accident in Ukraine in 1986 contaminated large parts of Belarus, northwestern Ukraine, and bordering Russian provinces. A case-control study in Belarus, with individual dose estimates, demonstrated a statistically significant link between thyroid cancer and environmental radiation dose from fallout related to the Chornobyl accident. REB and collaborators organized follow-up screening studies of benign and malignant thyroid disease among those exposed as children to fallout from the Chornobyl accident in Belarus and in Ukraine. The thyroid glands of approximately 12,000 subjects in each country have been screened biennially for four cycles in Ukraine and three cycles in Belarus. The projects are currently preparing to transition from active screening to other forms of follow-up using the existing national cancer registries. Cancer Mortality Among the Population Exposed to Radioactive Waste Released in to the Techa River by the Mayak Nuclear Facility in Russia Villagers living along the banks of the Techa River in Russia were exposed to chronic external and internal environmental radiation from radioactive waste released into the river by the Mayak nuclear facility. Cancer mortality is being evaluated in a cohort of approximately 30,000 people who received low to moderate radiation doses from the contaminated river. Current efforts focus on improving data quality, tracing the population for vital status information, and on statistical analyses and manuscript preparation. Associations between solid cancer and leukemia mortality and radiation dose have been observed. Cohort-based GWAS of Glioma We have initiated a cohort-based genome wide association study of glioma including 18 studies from the Cohort Consortium, with the aim of confirming gene regions associated with glioma risk, identifying new regions of genetic susceptibility that might be more apparent in a cohort setting, and conducting targeted gene-environment analyses based on the covariate data available from the cohorts. Contralateral Breast Cancer in AARP To study the risks for second cancers in breast cancer survivors we are evaluating changes in behavior after breast cancer diagnosis (such as smoking and alcohol consumption) in the AARP cohort. We then plan to evaluate the association between these modifiable risk factors and obesity and the risk of developing a contralateral breast cancer in these women. NHANES III: Prospective Vitamin Study The NHANES III data set with measured vitamin D levels on about 20,000 people is a unique resource that allows investigation of the relationship between vitamin D and specific causes of mortality. This cohort includes actual vitamin D measurements and about 2253 deaths, of which nearly 900 are cancer deaths. We previously published a study on the relationship between baseline vitamin D and all cancer mortality as of 2000, which found no association with cancer mortality, including by cancer site and within subgroups. Assessing risks accounting for an additional follow-up period, through 2006 we found no association of Vitamin D with cancer mortality, but some subgroups and outcomes showed adverse associations. Nordic Brain Collaboration Analyses from the NCI Adult Brain Tumor Study have identified possible risk factors for brain tumors including environmental factors such as exposure to lead, and genetic factors, including polymorphisms involved in lead metabolism. We plan to test these hypotheses using data from Nordic case-control studies of adult brain tumors for replication studies. Telomere Length and Risk of Glioma Recently published genome wide association studies of glioma indicate that the TERT gene, which codes for telomerase reverse transcriptase (an enzyme crucial to the maintenance of telomere length), is likely to be important in glioma etiology. We propose to examine the association between telomere length and the risk of glioma, , and will explore whether telomere length variation is modified by TERT polymorphisms that are highly associated with glioma risk. Thyroid Cancer Genetic Consortium (THYGENE) We are planning to perform a GWAS (Genome-Wide Association Studies) of differentiated thyroid cancer using 4,000 cases from several studies in THYGENE (including USRT) and 10,000 controls amassed from control series of other large studies, with replication in 1500 thyroid cancer cases and controls by remaining THYGENE consortium members. These studies include radiation- and non-radiation-exposed subjects. Thyroid Nodules as a Measure of Radiation Risk Among a Population of 3000 Residents in Kazakhstan Exposed as Children to Fallout from Nuclear Testing at the Semipalatinsk Test Site Thyroid nodule prevalence, determined by ultrasound screening, was used as the main outcome variable for evaluating the effects of environmental radiation fallout exposure in a population of 3000 village residents in Kazakhstan affected by radioactive fallout from nuclear bomb tests at the nearby Semipalatinsk Test Site during 1949-1962. A new dose-reconstruction algorithm, developed jointly by NCI and the Institute of Biophysics in Moscow, was used to estimate individual thyroid doses from external and internal sources of fallout-derived radiation, based mainly upon residential history and estimated consumption of milk from dairy animals grazing on contaminated pasture. Both external and internal dose were found to be significantly and independently associated with nodule prevalence. Current efforts, are focused on sources of dose uncertainty, especially those involving internal dose from radioactive isotopes of iodine ingested through the pasture-to-milk food chain. Polymorphic variants in 13 genes were studied for effect modification of the radiation dose-response relation and main effects on thyroid nodule risk. A variant in XRCCI was found to interact with radiation dose and thyroid nodule risk. Ultraviolet Sunlight Exposure, Ionizing Radiation, and Risk of Skin and Other Cancers Exposure to ultraviolet (UV) radiation from sunlight plays a predominant role in the etiology of melanoma and non-melanoma skin cancer, but the nature of the relationship is complex and not fully understood. In particular, the possible interaction with exposure to ionizing radiation is unclear. We recently completed questionnaire-based collection of lifetime UV sun-related radiation exposure from more than 70,000 U.S. radiologic technologists and have undertaken analyses to assess risks of specific forms of cancer in relation to this exposure. We also plan to evaluate whether skin cancer risks associated with occupational exposures to ionizing radiation might be modified by questionnaire-derived estimates of UV sun-related radiation exposures. UV exposure and Colorectal adenomas in the Fernald Community cohort We have begun to analyze data on the relationship between self-reported time outdoors throughout life and prospectively diagnosed colorectal adenomas.